Alzheimer’s Research: 100 years in the making

By: Lynne Hughes, B.Med.Sci., PhD, PMP | September 21, 2015

Despite decades of research, Alzheimer’s Disease continues to be one of the leading causes of death in the world today. According to data from the Alzheimer’s Association, one in three seniors in the United States dies with Alzheimer’s or another dementia related illness. Worldwide the number of people exhibiting dementia is forecast to rise to 131.5 million by 2050, and roughly 43 percent of these cases will require levels of care equivalent to that provided by nursing homes. And even though we have been aware of this disease for more than 100 years, we still cannot prevent it, cure it, or even slow it down.

As we recognize World Alzheimer’s Day, it is important to acknowledge these stark statistics, though it is equally important to acknowledge the progress that we have made. While we are far from curing Alzheimer’s Disease, recent shifts in research have begun to deliver promising results, and scientists are increasingly optimistic that one day in the not-too-distant future, this disease might finally fall under our control.

A new direction

Twenty years ago, clinical trials in this space were all focused on reacting to the disease. We didn’t consider patients treatable until they showed symptoms, and all efforts and research dollars were spent either trying to reverse the effect of the amyloid beta that clogs most Alzheimer’s patients’ brains, blocking cell-to-cell signaling at the synapses or on stimulating the remaining neurons to work more efficiently. Unfortunately, we had little success with these efforts, which ultimately led to the realization that the impact of this disease cannot be undone. We understand now that once a patient exhibits symptoms of Alzheimer’s Disease there is no going back.

But that realization led us down a different path to taking a preventive approach to Alzheimer’s. And we’ve made some remarkable discoveries. For example, in studies of healthy volunteers at risk of developing Alzheimer’s Disease, we have found the presence of amyloid beta decades before they become symptomatic. That means we can potentially identify the risk factors for Alzheimer’s 20 or 30 years in advance, giving us that much time to block the build-up of the plaque that leads to dementia, confusion and eventually death in the majority of these patients.

That has spurred many innovative research efforts, including a global initiative, developed by the European Prevention of Alzheimer's Disease Consortium (EPAD), which plans to draw thousands of patients from across the EU who are at risk for early Alzheimer’s, and funnel them into an adaptive trial where multiple biopharma companies can test and compare drugs in order to streamline the discovery process. Even with an 80 percent failure rate in the initial registry, the group expects to secure 6,000 patients for Phase II trials. Quintiles, along with several global biopharmaceutical companies are participating in these trials, and similar programs are being considered in the United States, Australia, Japan, and Canada.

Similarly, in March, GlaxoSmithKline, Johnson & Johnson, Biogen and other industry leaders announced plans to invest in a U.K. government-led fund designed to spotlight new approaches to dementia and Alzheimer's disease, investing in a $100 million effort help launch the Global Dementia Discovery Fund, which aims to unite industry, government and nonprofits in pursuit of novel medicines.

Some individual biopharma projects have also made some exciting advances. Earlier this year, Biogen announced that its experimental drug for Alzheimer’s disease, called aducanumab, sharply slowed the decline in mental function in a small clinical trial. The drug, which is designed to eliminate amyloid plaque in the brain, met and in some cases greatly exceeded expectations in terms of how much the highest dose slowed cognitive decline.

One possible reason for this initial success is that Biogen treated patients with either mild disease or early stage prodromal disease, where other trials that failed focused on later stage sufferers. This was just a small Phase I trial and there were indications of side effects among patients on the highest doses of the drug, but it has inspired hope across the research community. If we can identify and treat patients earlier in their disease journey before they are symptomatic, we may have a much greater chance of preventing or delaying its progress.

The research efforts being implemented today will take years to bring to fruition, but if they are successful, it is reasonable to believe that one day in the future we could have Alzheimer’s drugs that prevent/reduce amyloid growth, similar to the way Statins lower cholesterol levels, which could make Alzheimer’s a preventable disease, even for those at high risk.